Clinical Cross-Relaxation Imaging (CRI) at 3T magnetic field strength: methodolog

描述(申请人提供)：交叉弛豫成像(CRI)是磁共振成像(MRI)的一种新的定量方法，它允许测量和在体映射决定组织中水和大分子之间核磁相互作用的两个关键参数--大分子质子分数和交叉弛豫速率常数。该项目的总体目标是以3T成像平台为基础，针对系列临床应用定制CRI技术，并演示针对多发性硬化症(MS)的系列临床应用的可行性。该项目包含三个具体目标。在第一个目标中，将开发一种快速、准确、可靠的全脑CRI数据采集技术，用于系列临床应用。研究设计将包括将CRI与用于磁场和射频场校正的快速方法相结合，通过使用并行采集和分段回波平面信号读出来开发具有更高时间效率的序列，以及优化采样方案以实现最佳测量精度。在第二个目标中，将发展一种全面的交叉松弛图像处理和分析方法。这一方法将产生一系列潜在的生物标志物，用于在全球和区域水平上表征脑组织的病理变化。研究设计将包括图像处理算法的开发，该算法将结合参数图重建和组织分割，然后进行直方图分析。这将产生一系列量化指标，描述整个大脑、白质、灰质、病变和临床相关白质纤维束中交叉松弛参数的分布。在第三个目标中，将进行一项临床研究，以检验CRI衍生的定量成像生物标记物对MS引起的脑组织病理变化敏感的一般假设，并与患者的临床状态和病程相关。CRI将在50名MS患者(25名复发-缓解组和25名继发性进展组)和25名健康对照组中进行。将进行统计分析以比较不同组之间的前瞻性成像生物标记物，并测试成像生物标记物与普遍接受的多发性硬化症临床状态量表之间的关联。该项目的一个可能结果是，CRI将提供对MS脑组织病理性改变具有高度敏感性和特异性的新的生物标记物，这些生物标记物在治疗临床试验中作为替代终点具有很高的兴趣。在这个项目中获得的技术解决方案和基本知识将对CRI的其他潜在应用领域有用，如神经退行性疾病、血管疾病和肿瘤中枢神经系统疾病。与公众健康相关：该项目旨在开发一种新的定量磁共振成像方法，用于测量决定组织中水和大分子之间磁性相互作用的关键参数。这种方法有望对多发性硬化症和其他神经疾病的疾病进展和治疗效果进行监测。这项研究还将有助于更好地理解多发性硬化症患者残疾进展与神经组织损伤之间的关系。

DESCRIPTION (provided by applicant): Cross-relaxation imaging (CRI) is a new quantitative method of magnetic resonance imaging (MRI), which allows the measurement and in vivo mapping of two key parameters determining nuclear magnetic interactions between water and macromolecules in tissues - the macromolecular proton fraction and cross-relaxation rate constant. The general objectives of this project are to tailor the CRI technology to serial clinical usage based on a 3T imaging platform and to demonstrate the feasibility of serial clinical applications with a particular focus on multiple sclerosis (MS). The project contains three specific aims. In the first aim, a fast, accurate, and reliable whole-brain CRI data acquisition technology will be developed for serial clinical applications. The research design will include a combined application of CRI with fast methods for magnetic and radiofrequency field correction, development of the sequence with improved time efficiency by using parallel acquisition and segmented echo-planar signal readout, and optimization of a sampling scheme for the best measurement accuracy. In the second aim, a comprehensive methodology of cross-relaxation image processing and analysis will be developed. This methodology will produce a series of potential biomarkers for the characterization of pathological changes in brain tissues on both global and regional levels. The research design will include the development of the image processing algorithm, which will combine the reconstruction of parametric maps and tissue segmentation followed by histogram analysis. This will result in a series of quantitative metrics, characterizing distributions of cross-relaxation parameters in the entire brain, white matter, gray matter, lesions, and clinically relevant white matter fiber tracts. In the third aim, a clinical study will be conducted to test the general hypothesis that quantitative imaging biomarkers derived from CRI are sensitive to pathological changes in brain tissues caused by MS and are associated with the patients' clinical status and the course of the disease. CRI will be performed on groups containing 50 MS patients (25 with relapsing-remitting and 25 with secondary progressive disease course) and 25 healthy controls. Statistical analysis will be conducted to compare prospective imaging biomarkers between groups and to test associations between imaging biomarkers and commonly accepted MS clinical status scales. A probable outcome of this project is that CRI will provide new biomarkers with high sensitivity and specificity to pathological brain tissue changes in MS. Such biomarkers are of high interest as surrogate endpoints in therapeutic clinical trials. The technical solutions and basic knowledge gained in this project will be useful for other potential areas of CRI application, such as neurodegenerative, vascular, and neoplastic CNS disorders. PUBLIC HEALTH RELEVANCE: This project aims to develop a new quantitative method of magnetic resonance imaging for measurements of key parameters determining magnetic interactions between water and macromolecules in tissues. This method is expected to be highly beneficial for monitoring of disease progression and treatment effects in multiple sclerosis and other neurological disorders. This study also will lead to improved understanding of a relationship between disability progression and neural tissue damage in multiple sclerosis.